Abstract
ORMDL1, a member of the ORMDL protein family, is an endoplasmic reticulum membrane protein. Abnormal expression of ORMDL1 in various types of human cancers has attracted much attention in recent years. However, the function of ORMDL1 in ESCC has not been reported. The present study was the first to report that ORMDL1 can serve as a useful prognostic marker in ESCC. The methods used to assess the role of ORMDL1 in predicting the prognosis of ESCC were mainly bioinformatics analysis, WB and Immunohistochemistry. The abnormal expression of ORMDL1 in various types of cancers was determined using data from TCGA and GEO databases. In ESCC, we found that the expression level of ORMDL1 was significantly higher in tumor tissues than that in normal esophageal tissues (p < 0.001). The association between high level of ORMDL1 expression and poor prognosis was evaluated with Kaplan-Meier survival analysis. Univariate and multivariate Cox regression analyses were performed on both TCGA and our own samples to determine whether ORMDL1 is an independent prognostic factor for ESCC. Moreover, analysis of immune infiltration showed a significant connection between ORMDL1 expression and various immune cell subtypes, including T helper cells and neutrophils, underscoring its potential as a biomarker for poor prognosis. Western blot analysis further validated that the expression levels of ORMDL1 in esophageal squamous cell carcinoma (ESCC) tissues and cell lines are significantly greater compared to those in normal esophageal tissues and epithelial cell lines. This finding aligns with the outcomes observed in database analyses. By integrating multi-omics data with experimental findings from clinical samples, we hypothesize that ORMDL1 may contribute to the initiation and advancement of ESCC. Its elevated expression is not only associated with unfavorable prognosis but may also be involved in tumor immune evasion through its impact on the tumor immune microenvironment. Consequently, ORMDL1 has the potential to act as a promising molecular biomarker for diagnosing and assessing prognosis in ESCC, offering new avenues for research and targets for personalized therapies for ESCC.